Although epidemiological studies have established linkages between close personal relations and health, the pathways are not well-understood. This project will investigate the interactions among marital behavior, age, neuroendocrine and immune function, and their relationship to wound healing among 100 couples who range in age from 18 to 75. Three studies have demonstrated that stress has significant consequences for wound repair in humans. Early events in wound healing, particularly the first 24 hours, represent a critical period, and dysregulation during this interval potentiates problems later; thus, the immunological studies will focus on this stage as changes in two different types of wounds are examined. To separate the effects of the acute stress of a marital conflict from the chronic strains of marital dissatisfaction on wound healing, subjects will undergo an initial oral biopsy 3-4 weeks prior to a 26-hour admission to the General Clinical Research Center (GCRC). A second small wound will be placed in the hard palate shortly after GCRC admission, and a suction blister protocol will be initiated to provide a mechanism for studying the inflammatory responses in vivo. After induction of suction blisters, each couple will be asked to discuss an area of disagreement for half an hour, a procedure that can provoke significant endocrine and immunological changes. Thus,. The protocols provides for concurrent measurement of cytokines and leukocytes in blister chamber fluid and peripheral blood, serial evaluations of hormones relevant to wound healing, as well as the assessment of oral wound healing as a consequence of both acute and chronic stress. The proposed studies will: 1) assess the linkages among marital behavior, hormones, and production of pro-inflammatory cytokines, as well as the extent to which the stress of an acute conflict and gender mediate these relationships; 2) determine the relationships between hormones and production of pro-inflammatory cytokines from peripheral blood and blister chamber fluid, and the influence of age on these pathways; 3) assess relationships between cytokines from peripheral blood and blister chamber fluid and the healing of blister sites and oral wounds; and 4) determine the extent to which age interacts with marital distress to impair cytokine secretion and wound healing.